Safety and Feasibility of High-Pressure/High-Dose Pressurized Intraperitoneal Aerosol Chemotherapy (HP/HD-PIPAC) for Primary and Metastatic Peritoneal Surface Malignancies.

OBJECTIVE: The aim of this study was to evaluate the feasibility and perioperative safety of high-pressure/high-dose pressurized intraperitoneal aerosol chemotherapy (HP/HD-PIPAC) to manage peritoneal surface malignancies (PSM). METHODS: Retrospective analysis of a prospective database of about 130 consecutive patients scheduled for HP/HD-PIPACs for PSM. Doxorubicin plus cisplatin (PIPAC-C/D) or oxaliplatin (PIPAC-Ox) were nebulized into a constant capnoperitoneum of 20 mmHg at doses of 6, 30, or 120 mg/m2 of body surface area (BSA). Outcome criteria were perioperative complications (Clavien-Dindo). RESULTS: The median age of patients was 62 years (range 9-82), and the primary tumor site was of colorectal (CRC), upper gastrointestinal tract (UGI), unknown primary (CUP), malignant epithelioid mesothelioma of the peritoneum (MPM), hepato-pancreatic-biliary tract (HPB), and other origin in 30 (23.1%), 27 (20.8%), 16 (12.3%), 16 (12.3%), 6 (4.6%), and 35 (26.9%) patients, respectively. Abdominal access failed for a first, second, third, and fourth or more HP/HD-PIPAC in 12/130 (9.2%), 4/64 (6.3%), 6/40 (15.0%), and 2/33 (6.1%) patients. A total of 243 procedures were performed in 118 patients. No intraoperative complications related to increased capnoperitoneal pressure occurred, but an intraoperative bleeding complication was observed in 1/243 (0.4%) patients. The overall rate of postoperative procedure-related complications was 19.3% (47/243), while 15.3% (37/243), 1.6% (6/243), 1.6% (1/243), 0.4% (1/243), and 0.4% (1/243) were Grade I, II, III, IV, and V complications, respectively. CONCLUSIONS: Perioperative complications of HP/HD-PIPAC are comparable with standard pressure/dose PIPAC treatment protocols. Prospective studies are warranted to examine potential improvement in therapy outcomes.

Deletion of mTOR in liver epithelial cells enhances hepatic metastasis of colon cancer.

Activation of the mechanistic target of rapamycin (mTOR) pathway is frequently found in cancer, but mTOR inhibitors have thus far failed to demonstrate significant antiproliferative efficacy in the majority of cancer types. Besides cancer cell-intrinsic resistance mechanisms, it is conceivable that mTOR inhibitors impact on non-malignant host cells in a manner that ultimately supports resistance of cancer cells. Against this background, we sought to analyze the functional consequences of mTOR inhibition in hepatocytes for the growth of metastatic colon cancer. To this end, we established liver epithelial cell (LEC)-specific knockout (KO) of mTOR (mTORLEC ) mice. We used these mice to characterize the growth of colorectal liver metastases with or without partial hepatectomy to model different clinical settings. Although the LEC-specific loss of mTOR remained without effect on metastasis growth in intact liver, partial liver resection resulted in the formation of larger metastases in mTORLEC mice compared with wildtype controls. This was accompanied by significantly enhanced inflammatory activity in LEC-specific mTOR KO livers after partial liver resection. Analysis of NF-ĸB target gene expression and immunohistochemistry of p65 displayed a significant activation of NF-ĸB in mTORLEC mice, suggesting a functional importance of this pathway for the observed inflammatory phenotype. Taken together, we show an unexpected acceleration of liver metastases upon deletion of mTOR in LECs. Our results support the notion that non-malignant host cells can contribute to resistance against mTOR inhibitors and encourage testing whether anti-inflammatory drugs are able to improve the efficacy of mTOR inhibitors for cancer therapy. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Elevated levels of circulating osteopontin are associated with a poor survival after resection of cholangiocarcinoma.

BACKGROUND & AIMS: Cholangiocarcinoma (CCA) represents a primary hepatic malignancy with incidence and mortality rising globally. Surgical treatment has remained the only potentially curative treatment option, but it is still unclear which patients benefit most from extended liver surgery, highlighting the need for new pre-operative stratification strategies. Osteopontin is a secreted extracellular glyco-phosphoprotein that has been associated with inflammation, metabolic disorders and cancer. Here, we examined the potential of circulating osteopontin serum levels as a diagnostic or prognostic biomarker in patients with CCA undergoing extended liver surgery. METHODS: Osteopontin expression levels were analysed in human and murine CCA tumour samples, using semi-quantitative reverse transcriptase PCR and immunohistochemistry. Osteopontin serum concentrations were measured by enzyme-linked immunosorbent assay in 107 patients with CCA undergoing elective tumour resection as well as 55 healthy controls. Results were correlated with clinical data. RESULTS: Correlating with an upregulation in CCA tumour cells and the tumour stroma, serum levels of osteopontin were elevated in patients with cholangiocarcinoma compared to healthy controls and patients with primary sclerosing cholangitis. Importantly, pre- and postoperative elevations of osteopontin showed a striking association with poor postoperative survival. CONCLUSIONS: Serum osteopontin concentrations represent a promising prognostic biomarker in patients resectable CCA which could help to guide preoperative treatment decisions and to identify patients that will particularly benefit from extended liver surgery. Lay summary: Extended liver surgery is the only potentially curative treatment for patients with cholangiocarcinoma (CCA/biliary cancer), but it is currently unclear which patients benefit most from surgery. Detecting serum levels of osteopontin - a specific secreted glycoprotein involved in multiple human diseases - in CCA patients might help to identify those patients that particularly benefit from tumour resection.

Preoperative Embolization of the Celiac Axis or Common Hepatic Artery before Distal Pancreatectomy with Resection of the Celiac Axis.

Patients with locally advanced pancreatic cancer who undergo distal pancreatectomy with resection of the celiac axis (CA) are at risk for postoperative hepatic or gastric ischemia if collateral blood flow from the superior mesenteric artery (SMA) via the gastroduodenal artery is insufficient. This study presents a technique for preoperative angiographic evaluation of these collateral vessels by using an AMPLATZER Vascular Plug to temporarily occlude the CA or common hepatic artery while simultaneously performing digital subtraction angiography of the SMA. If collateral vessels are deemed sufficient, the plug can subsequently be released for permanent occlusion with the intent to enhance the blood flow in these collateral vessels.

A liver nodule in a patient transplanted for primary sclerosing cholangitis: an interdisciplinary diagnostic approach.

We report the case of a 53-year-old female patient who was transplanted with the liver of a 71-year-old male donor for advanced primary sclerosing cholangitis (PSC) and who additionally was diagnosed with a histologically non-classifiable colitis shortly before transplantation. Upon follow-up abdominal ultrasound 4 months after transplantation, a liver lesion measuring 16 × 23 mm was detected in the transplanted liver. This lesion had not been noticed immediately after transplantation and showed a pattern suspicious for malignancy in contrast-enhanced ultrasound. In line, a biopsy revealed the presence of a metastasis of an adenocarcinoma of colorectal origin, suggesting that a colitis- and PSC-associated colorectal cancer of the recipient might have been overseen upon the initial diagnostic workup. Despite two negative follow-up colonoscopies, this hypothesis was further supported by a strong positive signal in projection to the cecum in a subsequently performed PET/CT-scan. However, surgical resection of the right colon that was performed simultaneously with the atypical resection of the liver metastasis only revealed an inflamed diverticulum but no malignancy in the resected colon segment. Moreover, cytogenetic and molecular genetic testing on the resected specimens clearly attributed the metastasis to the male donor. On the one hand, this case underlines the necessity of endoscopic surveillance of patients with PSC and/or inflammatory bowel disease as well as the challenges in diagnosis of colitis-associated cancer. On the other hand, it shows that the acceptance of organs from elderly donors in times of organ shortage might be linked to an increased risk of donor transmitted malignancies.

Grade of donor liver microvesicular steatosis does not affect the postoperative outcome after liver transplantation.

BACKGROUND: The potential effect of graft steatosis on the postoperative liver function is discussed controversially. The present study aimed to evaluate the effect of the donor liver microvesicular steatosis on the postoperative outcome after liver transplantation. METHODS: Ninety-four patients undergoing liver transplantation at the University Hospital Aachen were included in this study. The patient cohort was divided into three groups according to the grade of microvesicular steatosis (MiS): MiS <30% (n=27), MiS 30%-60% (n=41) and MiS >60% (n=26). The outcomes after liver transplantation were evaluated, including the 30-day and 1-year patient and graft survival rates and the incidences of early allograft dysfunction (EAD) and primary nonfunction (PNF). RESULTS: The incidences of EAD and PNF did not differ significantly between the groups. We observed 5 cases of PNF, one occurred in the MiS <30% group and 4 in the MiS 30%-60% group. The 30-day and 1-year graft survivals did not differ significantly between groups. The 30-day patient survival rates were 100% in all groups. The 1-year patient survival rates were 94.4% in the MiS <30% group, 87.9% in the MiS 30%-60% group and 90.9% in the MiS >60% group. CONCLUSION: Microvesicular steatosis of donor livers has no negative effect on the postoperative outcome after liver transplantation.

In vivo imaging of antioxidant response element activity during liver regeneration after partial hepatectomy.

BACKGROUND: The nuclear factor-erythroid 2-related factor 2 (Nrf2) -antioxidant response element (ARE) pathway is important for the regulation of antioxidative stress response and detoxification. To activate the expression of its target genes, such as heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase (quinone) 1 (NQO1), Nrf2 binds to the ARE within the promoter region of these genes. Partial hepatectomy and consecutive liver regeneration lead to oxidative stress with activation of the Nrf2-ARE pathway. The aim of this study was to investigate ARE activity in vivo during liver regeneration after partial hepatectomy. MATERIALS AND METHODS: Transgenic ARE-luc mice were used. In these mice, the luciferase reporter gene is under the control of an ARE promoter element. Following 2/3 partial hepatectomy (PHx), mice underwent in vivo bioluminescence imaging up until the ninth postoperative day. In addition, liver tissue was analyzed by immunohistochemistry (Nrf2 and HO-1), quantitative reverse transcription-PCR (HO-1 and NQO1) and in vitro luminescence assays. RESULTS: Bioluminescence imaging revealed a significant increase in Nrf2-ARE activity after PHx. The signal maximum was recorded on the third day after PHx. Seven days postoperatively, the signal almost reached baseline levels. In immunohistochemistry, significantly more hepatocytes were positive for Nrf2 and HO-1 on the third postoperative day compared with baseline levels. The mRNA expression of HO-1 and NQO1 were significantly increased on day 3 as measured by qRT-PCR. CONCLUSIONS: This study demonstrated the time-dependent activation of the Nrf2-ARE system during liver regeneration in vivo. The transgenic ARE-luc mouse provided a convenient model for studying Nrf2-mediated gene expression noninvasively and may facilitate further experiments with therapeutic modulation of the antioxidative stress response.

Video-assisted hepatic abscess debridement.

BACKGROUND: Pyogenic liver abscesses are currently treated by either percutaneous computer tomography (CT)-guided drainage or by laparoscopic and a conventional liver resection when conservative treatment fails but may be associated with substantial morbidity and mortality. METHODS: A minimally invasive technique involving debridement of right liver abscesses was employed using a minimally invasive video-assisted hepatic abscess debridement (VAHD) after unsuccessful percutaneous CT-guided drainage. Clinical data, complication rates and outcomes of patients were recorded retrospectively. RESULTS: Between 2011 and 2014, VAHD was performed on 10 patients at two centres with no observed recurrence of a liver abscess. The median age of the patients was 57 years (range 42-78) with a median pre-operative size of a liver abscess of 78 mm (range 40-115). The median operation time was 47 min (range 23-75), and the median postoperative hospital stay was 9 days (range 7-69). One patient developed a subcutaneous abscess that required further surgery. No patient died, and there were no major complications related to the VAHD. CONCLUSIONS: Video-assisted hepatic abscess debridement is a feasible technique that shows promising results for the treatment of a recurrent right liver abscess.

The CUSA Clarity Soft Tissue Removal Study: Clinical Performance Investigation of the CUSA Clarity Ultrasonic Surgical Aspirator System for Soft Tissue Removal During Liver Surgery.

Background: Intraoperative blood loss has an unfavorable impact on the outcome of patients undergoing liver surgery. Today, the use of devices capable of minimizing this risk with high technical performance becomes mandatory. Into this scenario fits the CUSA® Clarity Ultrasonic Surgical Aspirator System. This prospective survey involving five liver surgery centers had the objective of investigating whether this innovative ultrasonic surgical aspirator is safe and effective in the transection of the liver parenchyma. Materials and Methods: This clinical study was a prospective, multicenter, single-arm Post-Market Clinical Follow-up study investigating 100 subjects who underwent liver surgery using the CUSA Clarity Ultrasonic Surgical Aspirator System at five centers during a period of 1 year and 8 months. After collecting all the patient's clinical information and instrument usage details, surgeons completed a brief survey giving their opinions on the performance of CUSA. Therefore, safety and efficacy outcomes were evaluated. Results: Surgeons had a 95% success rate in complete removal of the mass with an average overall operative time of 4 hours and 34 minutes. Overall, there were no complications or device deficiencies. Conclusion: The CUSA Clarity Ultrasonic Surgical Aspirator System performs well during liver surgery with a low complication rate. ClinicalTrials.gov Identifier: NCT04298268.

Short-term postoperative outcomes of lymphadenectomy for cholangiocarcinoma, hepatocellular carcinoma and colorectal liver metastases in the modern era of liver surgery: Insights from the StuDoQ|Liver registry.

INTRODUCTION: The clinical role of lymphadenectomy (LAD) as part of hepatic resection for malignancies of the liver remains unclear. In this study, we aimed to report on the use cases and postoperative outcomes of liver resection and simultaneous LAD for hepatic malignancies (HM). MATERIALS AND METHODS: Clinicopathological data from patients who underwent surgery at 13 German centers from 2017 to 2022 (n = 3456) was extracted from the StuDoQ|Liver registry of the German Society of General and Visceral Surgery. Propensity-score matching (PSM) was performed to account for the extent of liver resection and patient demographics. RESULTS: LAD was performed in 545 (16%) cases. The most common indication for LAD was cholangiocarcinoma (CCA), followed by colorectal liver metastases (CRLM) and hepatocellular carcinoma (HCC). N+ status was found in 7 (8%), 59 (35%), and 56 cases (35%) for HCC, CCA, and CRLM, respectively (p < 0.001). The LAD rate was highest for robotic-assisted resections (28%) followed by open (26%) and laparoscopic resections (13%), whereas the number of resected lymph nodes was equivalent between the techniques (p = 0.303). LAD was associated with an increased risk of liver-specific postoperative complications, especially for patients with HCC. CONCLUSION: In this multicenter registry study, LAD was found to be associated with an increased risk of liver-specific complications. The highest rate of LAD was observed among robotic liver resections.

Minimal Invasive Versus Open Surgery for Colorectal Liver Metastases: A Multicenter German StuDoQ|Liver Registry-Based Cohort Analysis in Germany.

Objective: To compare the outcome of minimally invasive liver surgery (MILS) to open liver surgery (OLS) for resection of colorectal liver metastases (CRLM) on a nationwide level. Background: Colorectal cancer is the third most common malignancy worldwide. Up to 50% of all patients with colorectal cancer develop CRLM. MILS represents an attractive alternative to OLS for treatment of CRLM. Methods: Retrospective cohort study using the prospectively recorded German Quality management registry for liver surgery. Propensity-score matching was performed to account for variance in the extent of resection and patient demographics. Results: In total, 1037 patients underwent liver resection for CRLM from 2019 to 2021. MILS was performed in 31%. Operative time was significantly longer in MILS (234 vs 222 minutes, P = 0.02) compared with OLS. After MILS, median length of hospital stay (LOS) was significantly shorter (7 vs 10 days; P < 0.001). Despite 76% of major resections being OLS, postoperative complications and 90-day morbidity and mortality did not differ. The Pringle maneuver was more frequently used in MILS (48% vs 40%, P = 0.048). After propensity-score matching for age, body mass index, Eastern Cooperative Oncology Group, and extent of resection, LOS remained shorter in the MILS cohort (6 vs 10 days, P < 0.001) and operative time did not differ significantly (P = 0.2). Conclusion: MILS is not the standard for resection of CRLM in Germany. Drawbacks, such as a longer operative time remain. However, if technically possible, MILS is a reasonable alternative to OLS for resection of CRLM, with comparable postoperative complications, reduced LOS, and equal oncological radicality.

A 7-gene signature of the recipient predicts the progression of fibrosis after liver transplantation for hepatitis C virus infection.

Fibrosis recurrence after liver transplantation (LT) for hepatitis C virus (HCV) is a universal event and strongly determines a patient's prognosis. The recipient risk factors for fibrosis recurrence are still poorly defined. Here we assess a genetic risk score as a predictor of fibrosis after LT. The cirrhosis risk score (CRS), which comprises allele variants in 7 genes (adaptor-related protein complex 3 S2, aquaporin 2, antizyme inhibitor 1, degenerative spermatocyte homolog 1 lipid desaturase, syntaxin binding protein 5-like, toll-like receptor 4, and transient receptor potential cation channel M5), was calculated for 137 patients who underwent LT for HCV infection and experienced HCV reinfection of the graft. The patients were stratified into 3 CRS categories: <0.5, 0.5 to 0.7, and >0.7. All patients underwent protocol biopsy after LT (median follow-up = 5 years), and liver fibrosis was assessed according to the Desmet and Scheuer score. The data were analyzed with univariate and multivariate analyses. The results showed that the highest CRS category was strongly associated with the presence of F2 or F3 fibrosis in protocol biopsy samples 1, 3, and 5 years after LT (P = 0.006, P = 0.001, and P = 0.02, respectively). Overall, 75.0% of the patients with a CRS > 0.7 developed at least F2 fibrosis, whereas 51.5% developed F3 fibrosis during follow-up. The predictive value of the CRS for fibrosis progression was independent of known clinical risk factors, including the age of the donor, the sex of the recipient, and the occurrence of acute rejection. A Kaplan-Meier analysis confirmed the prognostic value of the CRS with respect to the recurrence of severe liver fibrosis in HCV-infected patients after LT (log rank = 6.23, P = 0.03). In conclusion, the genetic signature of the recipient predicts the likelihood of severe liver fibrosis in the graft after HCV recurrence. The CRS might help with early clinical decision making (eg, the selection of patients for antiviral therapy after LT).

Serum chemokine CXC ligand 10 (CXCL10) predicts fibrosis progression after liver transplantation for hepatitis C infection.

UNLABELLED: The recurrence of liver fibrosis after liver transplantation (LT) for hepatitis C virus (HCV) infection is responsible for graft loss and patient mortality. Although the contribution of the immune system to fibrosis recurrence is anticipated, systematic studies evaluating immune parameters as predictive markers of allograft fibrosis are lacking. The infiltration of immune cells into the graft is governed by chemokines. Here we assessed the predictive value of serum levels of chemokines [chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10, CXCL11, and chemokine (C-C motif) ligand 2 (CCL2)] with respect to fibrosis recurrence after LT in 90 HCV-infected organ recipients. Chemokines were determined within the first and third years after LT and were correlated with histological fibrosis progression in protocol biopsy samples at 1, 3, 5, and 7 years (median follow-up = 3 years). The association of chemokines with fibrosis progression was assessed by univariate and multivariate analyses and by Cox regression analysis. The results for the analyzed chemokines showed that CXCL10 levels in the first year after LT were strongly associated with early fibrosis recurrence (P = 0.005) independently of risk confounders (including the donor age, HCV viral load, HCV genotype, acute rejection, and inflammatory activity). As assessed by Cox regression analysis, a CXCL10 serum level ≤ 140 pg/mL was significantly predictive of the absence of F2 fibrosis (P = 0.001), whereas a level ≤ 220 pg/mL early after LT predicted the absence of F3 fibrosis during follow-up (P = 0.035). CONCLUSION: CXCL10 is an independent biomarker of the recurrence of significant fibrosis after LT for HCV infection. These results might guide patients' care after transplantation and help us to select optimal candidates for antiviral therapy post-LT.

Antiviral treatment of patients with recurrent hepatitis C after liver transplantation with pegylated interferon.

BACKGROUND: The recurrence of hepatitis C virus (HCV) after liver transplantation (OLT) leads to recurrent cirrhosis in up to 40% of patients. AIMS: To identify patients who profit the most from antiviral therapy and to delineate whether early treatment after OLT is effective to reach sustained virological response (SVR), we analyzed factors associated to SVR during pegylated interferon/ribavirin (PegIFN/RBV) therapy. METHODS: A retrospective analysis of efficiency and viral decline kinetics in 83 HCV-infected liver transplant recipients who received therapy with PegIFN/RBV was carried out. RESULTS: Forty-one of 83 (49.4%) patients became HCV RNA-negative. SVR was achieved in 26/83 (31.3%) patients. Viral decline of at least 2 log 10 (n = 47) at week 12 was significantly associated with an end-of-treatment (EOT) response. Eleven early viral response patients were not able to clear HCV RNA, whereas five patients without a 2 log decline achieved SVR. The highest predictive value for SVR was an undetectable viremia at week 24 (92%). CONCLUSIONS: The outcome of antiviral combination therapy for HCV reinfection after OLT can be best predicted by week-24 virologic response. The high SVR rates in patients with detectable HCV RNA at week 12 might suggest a prolonged treatment protocol in liver transplant recipients.

Prolonged Survival of a Patient with Advanced-Stage Combined Hepatocellular-Cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (cHCC/CCA) represents a rare type of primary liver cancer with a very limited prognosis. Although just recently genomic studies have contributed to a better understanding of the disease's genetic landscape, therapeutic options, especially for advanced-stage patients, are limited and often experimental, as no standardized treatment protocols have been established to date. Here, we report the case of a 38-year-old male patient who was diagnosed with extensive intrahepatic cHCC/CCA in an otherwise healthy liver without signs of chronic liver disease. An interdisciplinary stepwise therapeutic approach including locoregional liver-targeted therapy, systemic chemotherapy, liver transplantation, surgical pulmonary metastasis resection, and next-generation sequencing-based targeted therapy led to a prolonged overall survival beyond 5 years with an excellent quality of life. This case report comprises several provocative treatment decisions that are extensively discussed in light of the existing literature on this rare but highly aggressive malignancy.

Erythropoietin reduces ischemia-reperfusion injury after liver transplantation in rats.

Human recombinant Erythropoietin (rHuEpo) has recently been shown to be a potent protector of ischemia- reperfusion injury in warm-liver ischemia. Significant enhancement of hepatic regeneration and survival after large volume partial hepatic resection has also been demonstrated. It was the aim of this study to evaluate the capacities of rHuEpo in the setting of rat liver transplantation. One-hundred-and-twenty Wistar rats were used: 60 recipients received liver transplantation following donor organ treatment (60 donors) with either 1000 IU rHuEpo or saline injection (controls) into portal veins (cold ischemia 18 h, University of Wisconsin (UW) solution). Recipients were allocated to two groups, which either received 1000 IU rHuEpo at reperfusion or an equal amount of saline (control). Animals were sacrificed at defined time-points (2, 4.5, 24, 48 h and 7 days postoperatively) for analysis of liver enzymes, histology [hematoxylin-eosin (HE) staining, periodic acid Schiff staining (PAS)], immunostaining [terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Hypoxyprobe] and real-time polymerase chain reaction (RT-PCR) of cytokine mRNA (IL-1, IL-6). Lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) values were significantly reduced among the epo-treated animals 24 and 48 h after liver transplantation (LT). The TUNEL and Hypoxyprobe analyses as well as necrotic index evaluation displayed significant reduction of apoptosis and necrosis in rHuEpo-treated graft livers. Erythropoietin reduces ischemia-reperfusion injury after orthotopic liver transplantation in rats.

Erythropoietin promotes hepatic regeneration after extended liver resection in rats.

BACKGROUND AND AIM: It has been proven in various animal studies that recombinant human erythropoietin (rHuEPO) protects renal, cardiac and neuronal, as well as hepatic, tissue from ischemia, and promotes regeneration of adult central nervous system neurons. To date, no data are available as to whether rHuEPO has the ability to stimulate liver regeneration after liver resection. METHODS: Rats undergoing 70% or 90% hepatectomy received an intraportalvenous administration (i.p.) of rHuEPO prior to resection or a subcutaneous injection (s.c.) for 3 days postoperatively, control animals were treated with surgery and saline injection only. Regeneration capacity of remnant livers was studied over 7 days by histology and immunohistochemistry (Ki-67, proliferating cell nuclear antigen [PCNA]). Polymerase chain reaction was carried out to measure transforming growth factor beta (TGF-beta), hypoxia induced factor (HIF), signal transducing activator 3 and vascular endothelial growth factor. RESULTS: Ten-day survival in rats undergoing 90% hepatectomy significantly increased in i.p.-pretreated animals. After 70% hepatectomy the mitotic index was significantly increased in both rHuEPO-treated groups. These data were confirmed by PCNA and Ki-67 expression, which was significantly increased in the treated groups 24 h and 2 days after liver resection. TGF-beta and HIF mRNA both were upregulated in control animals 3 h after surgery. CONCLUSION: rHuEPO effectively increased liver regeneration in rats after 70% liver resection and enhanced survival after 90% hepatectomy. Thus, rHuEPO may increase the regenerative capacity after major hepatectomy.

Impact of liver volume and liver function on posthepatectomy liver failure after portal vein embolization- A multivariable cohort analysis.

BACKGROUND: Liver failure remains a life-threatening complication after liver resection, and is difficult to predict preoperatively. This retrospective cohort study evaluated different preoperative factors in regard to their impact on posthepatectomy liver failure (PHLF) after extended liver resection and previous portal vein embolization (PVE). METHODS: Patient characteristics, liver function and liver volumes of patients undergoing PVE and subsequent liver resection were analyzed. Liver function was determined by the LiMAx test (enzymatic capacity of cytochrome P450 1A2). Factors associated with the primary end point PHLF (according to ISGLS definition) were identified through multivariable analysis. Secondary end points were 30-day mortality and morbidity. RESULTS: 95 patients received PVE, of which 64 patients underwent major liver resection. PHLF occurred in 7 patients (11%). Calculated postoperative liver function was significantly lower in patients with PHLF than in patients without PHLF (67 vs. 109 µg/kg/h; p = 0.01). Other factors associated with PHLF by univariable analysis were age, future liver remnant, MELD score, ASA score, renal insufficiency and heart insufficiency. By multivariable analysis, future liver remnant was the only factor significantly associated with PHLF (p = 0.03). Mortality and morbidity rates were 4.7% and 29.7% respectively. CONCLUSION: Future liver remnant is the only preoperative factor with a significant impact on PHLF. Assessment of preoperative liver function may additionally help identify patients at risk for PHLF.

Influence of basiliximab induction therapy on long term outcome after liver transplantation, a prospectively randomised trial.

BACKGROUND: In OLT induction therapy with interleukin-2-receptor antibodies is often applied as part of the standard immunosuppression protocol. It was the aim of this study to determine if Basilixirnab mduction therapy serves to reduce the incidence of acute rejection episodes and improves graft function and survival in the long term after OLT. MATERIAL/METHODS: We prospectively analysed 99 patients transplanted at our institution (1997-2000). Patients were randomised to two study groups: 51 patients received Basiliximab induction combined with Calcineurin inhibitors and steroids, 48 patients received CNIs and steroids only. Incidence and severity of rejection, graft and patient survival and intensity of long-term immunosuppression were analysed. Frequency of CNI and steroid induced adverse effects were recorded. RESULTS: In our patient collective we could not detect a significant impact of Basiliximab induction therapy on the fre queny of acute or chronic rejection. CNI levels were almost identical in both groups; graft and patient survival rates were not influenced by the application of induction therapy. CONCLUSIONS: In our patient collective induction therapy does not have a general positive influence on the post transplant course. A slight improvement in long term renal function could be detected for Basiliximab treated patients.